Sürdürülebilir Kalkınma Amaçları
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- MakaleAçık Erişim2026A multi-evidence computational and experimental strategy for Silene nerimaniae: combining phytochemical characterization, bioactivity assessment, and ADEFRank-HCT-116-based metabolite prioritization
Erharman, Ahmet; Yagi, Sakina; Uba, Abdullahi Ibrahim; Nikolic, Filip; Gasic, Uros; Acar, Mikail; Dogan, Nurettin; Koyuncu, Ismail; Yapici, Ismail; Gulcin, Ilhami
This study presents the first comprehensive evaluation of the phytochemical composition, antioxidant properties, enzyme inhibitory effects, and cytotoxic potential of Silene nerimaniae G.E.Gen & ccedil;, Kandemir & & Idot;.Gen & ccedil; (family Caryophyllaceae). Ethyl acetate, acetone, 70% acetone, and aqueous extracts were obtained from the aerial parts of the plant through maceration. Among the tested extracts, the acetone extract contained the highest total phenolic (24.37 mg GAE per g) and flavonoid (24.64 mg RE per g) contents. LC-MS analysis identified 52 bioactive constituents, including sugars, organic acids, phenolic acids, flavonoids, and fatty acids. The aqueous extract demonstrated the strongest radical scavenging activity against DPPH (23.02 mg TE per g) and ABTS (55.76 mg TE per g), as well as the highest Fe3+ reducing power (37.53 mg TE per g). In combination with the acetone extract, it also exhibited notable Cu2+ reducing activity (47.78 mg TE per g). Regarding enzyme inhibition, the ethyl acetate, acetone, and hydroacetone extracts displayed the strongest inhibitory activities against acetylcholinesterase (1.87 mg GALA per g), butyrylcholinesterase (2.92 mg GALA per g), and tyrosinase (60.44 mg KAE per g), respectively. All three extracts also inhibited alpha-amylase activity within the range of 0.73-0.77 mmol ACAE per g (p >= 0.05). In addition, the hydroacetone extract showed considerable inhibition of human carbonic anhydrase isoenzymes I (IC50 = 38.78 mu g mL-1) and II (IC50 = 19.59 mu g mL-1). The ethyl acetate extract exhibited the strongest cytotoxic effect against the colorectal cancer cell line HCT-116, with an IC50 value of 0.639 mu g mL-1 and a selectivity index of 1.7. To contextualize this HCT-116-associated activity at the metabolite level, an ADEFRank-HCT116 (abundance-domain-evidence fusion ranking) workflow was applied by integrating EtOAc abundance, HCT-116-oriented QSAR evidence, applicability-domain confidence, and structure-assignment reliability. This analysis prioritized diosmetin, luteolin, eriodyctiol, acacetin, and isorhamnetin as core candidates for structure-based follow-up. Molecular docking screening predicted favorable docking profiles for the prioritized candidates, while 100 ns molecular dynamics simulations were used to assess the dynamic stability of the representative luteolin-PI3K alpha, diosmetin-AKT1, and isorhamnetin-GSK-3 beta complexes. Taken together, these results indicate that S. nerimaniae may represent a valuable source of active compounds for various functional nutraceutical, cosmetic and pharmaceutical uses.
- MakaleAçık Erişim2026Chemical profiling, biological evaluation, and QSAR-informed metabolite prioritization of Hypericum ekerii: a first report on antioxidant, enzyme inhibitory, and cytotoxic activities
Zengin, Gokhan; Yagi, Sakina; Cetiz, Mehmet Veysi; Uba, Abdullahi Ibrahim; Nikolic, Filip; Gasic, Uros; Balos, Mehmet Maruf; Erharman, Ahmet; Dogan, Nurettin; Koyuncu, Ismail
Hypericum ekerii Y & uuml;ce and Ayta & ccedil;, first described in 2017, remains poorly characterized in terms of its phytochemical composition and biological properties. This study investigated aerial-part extracts of H. ekerii prepared with ethyl acetate, acetone, 70% acetone-water, and water. The hydroacetone extract showed the highest total phenolic and flavonoid contents. LC/MS analysis enabled the annotation of 99 constituents, including phenolic acids, flavonoids, xanthones, anthraquinones, and acylphloroglucinols. The hydroacetone extract exhibited the strongest radical-scavenging and reducing activities, whereas acetone and ethyl acetate extracts showed the highest metal-chelating capacity. In enzyme assays, hydroacetone was the most active extract against acetylcholinesterase, tyrosinase, and hCA II, while ethyl acetate showed greater inhibition of butyrylcholinesterase and hCA I. The aqueous extract was the most active against alpha-glucosidase, and hydroacetone and ethyl acetate showed comparable alpha-amylase inhibition. Cytotoxicity remained limited overall; the lowest IC50 value was observed for the ethyl acetate extract against HCT-116 cells (95.09 & micro;g mL-1), with weak selectivity (SI = 1.2). A QSAR-informed prioritization framework identified myricetin as the leading cross-layer candidate, p-coumaric acid as a target-specific priority metabolite, and ellagic acid, quercetin, and caffeic acid as antioxidant-priority candidates. Molecular docking supported favorable binding profiles for selected metabolites, while molecular dynamics simulations were used to assess the stability of representative complexes. Overall, H. ekerii appears to be a chemically diverse species with notable antioxidant and enzyme-inhibitory potential, providing a focused basis for future compound-level validation.
- MakaleYalnız künye2026Chemical characterization and bioactivity assessment of Erodium cedrorum subsp. salmoneum extracts supported by in silico analysis
Yagi, Sakina; Zengin, Gokhan; Zoltan, Cziaky; Jeko, Josef; Ivashchanka, Yahor; Turecka, Katarzyna; Halasa, Rafal; Gucwa, Magdalena; Kochan-Jamrozy, Kinga; Stefanowicz-Hajduk, Justyna
The growing interest in natural products, particularly as food additives and pharmaceutical raw materials, is making research into discovering new sources especially important. Erodium cedrorum subsp. salmoneum (family Geraniaceae) is used traditionally to cure many ailments like diabetes and gastro-intestinal diseases. Within this background, the current study was designed to investigate, for the first time, the chemical composition, antioxidant and enzyme inhibitory poroperties of different extracts from the aerial parts and roots of E. cedrorum. Results revealed that the aqueous extract of the aerial parts accumulated the highest total phenolic (85.35 mg GAE/g) and flavonoids (28.65 mg RE/g) contents. A total of 61 and 45 compounds, belonging mainly to phenolic acids and flavonoids, were tentatively identified in the aerial parts and roots extracts respectively. The aqueous extract from the aerial parts exerted the highest antiradical, ions reducing and chelation properties. The EtOH and 70% EtOH extracts of the two organs recorded the best anti-acetylcholinesterase activity (2.18 -2.41 mg GALAE/g; p >= 0.05) while those of the roots recorded respectively the best anti-butyrylcholinesterase and antityrosinase activities. The most potent antibacterial activity was exhibited by the 70% EtOH extracts from aerial parts and the pure EtOH extracts from roots. In contrast, ethyl acetate extracts from both plant parts showed only marginal activity. Among the tested strains, the highest susceptibility was observed against C. sporogenes ATCC 19404, C. bifermentans ATCC 638, S. aureus ATCC 6538, S. aureus ATCC 43300 (MRSA), C. diphtheriae PCM 506, and H. pylori ATCC 43504. The extracts were also examined for their anti-cancer potential on the HeLa, AGS and SKOV-3 cell lines, as well as a non-cancerous cell line. The ethyl acetate extract of the roots exhibited the most potent anti-cancer activity, with the lowest IC50 values. In addition, selected top-ranked complexes against AChE, alpha-amylase, representative bacterial and oncogenic targets were further evaluated by molecular docking and 100 ns molecular dynamics (MD) simulations, indicating overall conformational stability and persistent binding. In conclusion, these results position E. cedrorum as a valuable natural source of antioxidant and enzyme-inhibitory agents, meriting further exploration for drug development purposes.
- MakaleAçık Erişim2026Chemical Constituents and Biological Potentials of Teucrium scordium subsp. scordioides Extracts: In Vitro Experimental and In Silico Perspectives
Akgul, Bengusu Hacer; Yagi, Sakina; Cetiz, Mehmet Veysi; Saka, Enver; Zengin, Gokhan; Llorent-Martínez, Eulogio J.; Gómez-Torres, Marina; Yapici, Ismail; Gulcin, Ilhami; Yildiztugay, Evren
This study was undertaken to examine, for the first time, the antioxidant and enzyme inhibitory properties of several extracts obtained from the aerial parts of Teucrium scordium subsp. scordioides (Schreb.) Arcang (family: Lamiaceae). Among the extracts, the EtOH extract contained the highest total phenolic (89.96 mg GAE/g) and flavonoid (45.74 mg RE/g) contents. Phenylethanoid glycosides were predominant, particularly in the ethanol and aqueous extracts, and teucroside/forsythoside B and verbascoside/forsythoside A were tentatively identified as the major compounds. EtOH and 70% EtOH extracts showed comparable (p > 0.05) anti-DPPH activity (201.89 and 188.52 mg TE/g), Cu++ (562.81 and 547.88 mg TE/g), and Fe+++ (329.13 and 320.08 mg TE/g) reducing capacities. The EtOH extract showed the best antityrosinase activity (72.00 mg KAE/g). The EtOAc extract inhibited human carbonic anhydrase (CA) isoenzymes I and CAII (IC50 = 26.86 and 65.37 mu g/mL, respectively). Complementary in silico analyses of the major phenylethanoid and flavonoid glycosides supported their possible multitarget interaction patterns and identified the Forsythoside A-BChE complex as a computationally favorable model for future experimental validation. Overall, these findings indicate that T. scordium subsp. scordioides may represent a natural source of antioxidants and enzyme inhibitors for use in different health-promoting formulations.
- MakaleAçık Erişim2026Beyond the fruit: phenolic composition, cytotoxicity, antioxidant, and multi-enzyme inhibitory activity of twig and leaf extracts from four understudied Turkish Rosa species
Salehi, Hajar; Terzic, Milena; Ak, Gunes; Zengin, Gokhan; Swiatek, Lukasz; Salwa, Kinga; Yapici, Ismail; Gulcin, Ilhami; Yildiztugay, Evren; Lucini, Luigi
The phytochemical profile and multi-target bioactivity of four Turkish Rosa species, R. canina, R. hemisphaerica, R. horrida, and R. pulverulenta, were evaluated across vegetative organs (twigs and leaves) and three solvent polarities (ethyl acetate (EA), methanol (MeOH), water), in total 24 extracts. Untargeted Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-QTOF-MS) metabolomics, along with total phenolic (TPC) and flavonoid (TFC) content, six antioxidant assays and inhibition of seven enzymes were determined. Twig EA extracts displayed unexpectedly high TPC (83-105 mg gallic acid equivalent (GAE) per g) and TFC (35-47 mg rutin equivalent (RE) per g), indicative of selective aglycone flavonoid enrichment. The phenolic profiles identified 337 putative compounds, of which 60.84% belonged to the flavonoid class. The semi-quantitative analysis also indicates that methanol and water extracts had higher quantities of glycosylated flavonoids and phenolic acids, while EA extracts were richer in lignans, especially R. horrida-leaf-EA (1743.25 & micro;g SE per g DW), and polyphenols. In enzyme inhibition assays, EA extracts demonstrated consistent multi-target activity: AChE inhibition (up to 2.49 mg galantamine equivalent (GALAE) per g), BChE inhibition (up to 4.44 mg GALAE per g), tyrosinase inhibition (up to 63.58 mg kojic acid equivalent (KAE) per g), alpha-amylase inhibition (up to 0.72 mmol acarbose equivalent ACAE per g), and carbonic anhydrase inhibition (CA I IC50 as low as 12.17 & micro;g mL-1). The R. hemisphaerica-twig-EA extract showed highly selective cytotoxic activity against A375 cells, with a 50% cytotoxic concentration (CC50) of 3.22 & micro;g mL-1 and an SI of 73.95, compared to VERO cells. This is the first report of carbonic anhydrase inhibition, BChE-selective activity, cytotoxicity, and comprehensive enzyme-inhibitory data for R. hemisphaerica, R. horrida, and R. pulverulenta. These findings reframe the phytopharmacological potential of Turkish Rosa species beyond their traditionally studied fruit.
- MakaleAçık Erişim2025Evaluation of Antioxidant and Enzyme Inhibition Properties of Siran Propolis: Correlations With Phenolic Content Determined by LC–MS/MS
Balci, Neslihan; Aslan, Kubra; Erturk, Adem; Gulcin, Ilhami
This study evaluates the antioxidant activity, enzyme inhibition potential, and phenolic composition of ethanolic Siran propolis extract. Antioxidant capacity was measured using reducing power (CUPRAC, FRAP, and Fe3+-reducing) and radical scavenging (DPPH·, ABTS·+, and DMPD·+) assays. The extract showed strong reducing ability, surpassing standard antioxidants in CUPRAC and FRAP assays, correlating with high ferulic acid (40.40 mg/g) and p-coumaric acid (88.60 mg/g) levels identified by LC–MS/MS. While it demonstrated notable DPPH· scavenging (IC50: 30.14 μg/mL), ABTS·+ activity was weaker (IC50: 272.44 μg/mL). Enzyme inhibition assays indicated effective inhibition of α-glycosidase, AChE (IC50: 2.15 μg/mL), hCA I, and hCA II. Notably, AChE inhibition was stronger than the standard tacrine inhibitor (IC50: 8.82 μg/mL), suggesting neuroprotective potential. The observed bioactivities are attributed to synergistic effects of phenolic acids and flavonoids, including quercetin, luteolin, taxifolin, and resveratrol. These findings highlight Siran propolis as a promising natural antioxidant and enzyme inhibitor source with potential therapeutic applications and food formulations.
- MakaleYalnız künye2021Inhibition Profiles of Some Symmetric Sulfamides Derived from Phenethylamines on Human Carbonic Anhydrase I, and II Isoenzymes
Topal, Fevzi; Aksu, Kadir; Gulcin, Ilhami; Tümer, Ferhan; Goksu, Süleyman
In this work, the inhibitory effect of some symmetric sulfamides derived from phenethylamines were determined against human carbonic anhydrase (hCA) I, and II isoenzymes, and compared with standard compound acetazolamide. IC50 values were obtained from the Enzyme activity (%)-[Symmetric sulfamides] graphs. Also, Ki values were calculated from the Lineweaver-Burk graphs. Some symmetric sulfamides compounds (11–18) demonstrated excellent inhibition effects against hCA I, and II isoenzymes. These compounds demonstrated effective inhibitory profiles with IC50 values in ranging from 21.66–28.88 nM against hCA I, 14.44–30.13 nM against hCA II. Among these compounds, the best Ki value for hCA I (Ki: 8.34±1.60 nM) and hCA II (Ki: 16.40±1.00 nM) is compound number 11. Besides, the IC50 value of acetazolamide used as a standard was determined as hCA I, hCA II 57.75 nM, 49.50 nM, respectively. Moreover, in silico ADME-Tox study showed that all synthesized compounds (11–18) had good oral bioavailability in light of Jorgensen's rule of three, and of Lipinski's rule of five.
- MakaleAçık Erişim2021LC-HRMS Profiling and Antidiabetic, Anticholinergic, and Antioxidant Activities of Aerial Parts of Kinkor (Ferulago stellata)
Kiziltas, Hatice; Bingol, Zeynebe; Gören, Ahmet Ceyhan; Kose, Leyla Polat; Durmaz, Lokman; Topal, Fevzi; Alwasel, Saleh H.; Gulcin, Ilhami
Kinkor (Ferulago stellata) is Turkish medicinal plant species and used in folk medicine against some diseases. As far as we know, the data are not available on the biological activities and chemical composition of this medicinal plant. In this study, the phytochemical composition; some metabolic enzyme inhibition; and antidiabetic, anticholinergic, and antioxidant activities of this plant were assessed. In order to evaluate the antioxidant activity of evaporated ethanolic extract (EEFS) and lyophilized water extract (WEFS) of kinkor (Ferulago stellata), some putative antioxidant methods such as DPPHGreek ano teleia scavenging activity, ABTS(center dot+) scavenging activity, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+)-binding activities were separately performed. Furthermore, ascorbic acid, BHT, and alpha-tocopherol were used as the standard compounds. Additionally, the main phenolic compounds that are responsible for antioxidant abilities of ethanol and water extracts of kinkor (Ferulago stellata) were determined by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Ethanol and water extracts of kinkor (Ferulago stellata) demonstrated effective antioxidant abilities when compared to standards. Moreover, ethanol extract of kinkor (Ferulago stellata) demonstrated IC50 values of 1.772 mu g/mL against acetylcholinesterase (AChE), 33.56 +/- 2.96 mu g/mL against alpha-glycosidase, and 0.639 mu g/mL against alpha-amylase enzyme respectively.
- MakaleAçık Erişim2021Antidiabetic, anticholinergic and antioxidant activities of aerial parts of shaggy bindweed (Convulvulus betonicifolia Miller subsp.) - profiling of phenolic compounds by LC-HRMS
Bingol, Zeynebe; Kiziltas, Hatice; Gören, Ahmet C.; Kose, Leyla Polat; Topal, Meryem; Durmaz, Lokman; Alwasel, Saleh H.; Gulcin, Ilhami
In order to evaluate the antioxidant activity of evaporated ethanolic extract (EESB) and lyophilized water extract (WESB) of Shaggy bindweed (Convulvulus betonicifolia Mill. Subs), some putative antioxidant methods such as DPPH. scavenging activity, ABTS(center dot)(-) scavenging effect, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+) binding activities were separately performed. Also, ascorbic acid, alpha-tocopherol and BHT were used as the standard compounds. Additionally, some phenolic compounds that responsible for antioxidant abilities of EESB and WESB were screened by liquid chromatography-high resolution mass spectrometry (LC-HRMS). At the same concentration, EESB and WESB demonstrated effective antioxidant abilities when compared to standards. In addition, EESB demonstrated IC50 values of 1.946 mu g/mL against acetylcholinesterase (AChE), 0.815 mu g/mL against alpha-glycosidase and 0.675 mu g/mL against alpha-amylase enzymes.
- MakaleAçık Erişim2019Anticholinergic, antidiabetic and antioxidant activities of cinnamon (cinnamomum verum) bark extracts: polyphenol contents analysis by LC-MS/MS
Gulcin, Ilhami; Kaya, Ruya; Goren, Ahmet C.; Akincioglu, Hulya; Topal, Meryem; Bingol, Zeynebe; Cakmak, Kader Cetin; Sarikaya, Sevim B. Ozturk; Durmaz, Lokman; Alwasel, Saleh
Ethanolic (EEC) and aqueous (WEC) extracts of cinnamon (Cinnamomum verum) were evaluated for their antioxidant profiles by eight distinguished bioanalytical antioxidant methods. Their inhibitory effects were tested against some enzymes including acetylcholinesterase, butyrylcholinesterase, alpha-glycosidase and alpha-amylase, which linked to different diseases. Additionally, the antioxidant properties were determined and polyphenolic compositions of the both extracts were evaluated by LC-MS/MS analysis. According to the LC-MS/MS experiments, thirteen compounds were found in WEC and EEC. Also, p-hydroxybenzoic acid (321.1 mg/kg extract), p-coumaric acid (291.4 mg/kg extract), and pyrogallol (142.4 mg/kg extract) were found to be the most abundant ingredients in the WEC. On the other hand, pyrogallol (264.3 mg/kg extract), ferulic acid (224.7 mg/kg extract) and p-coumaric acid (170.2 mg/kg extract) were found as the most plentiful chemicals in the EEC. For the estimation of the antioxidant capacities of the both extracts (WEC and EEC), DPPH center dot and ABTS(center dot+) scavenging activities, as well as Fe3+-Fe2+, and Cu2+-Cu+ reducing assays were studied. The IC50 values of the WEC and EEC indicated that they were potent effective DPPH center dot (21. 25 and 15.71 mu g/mL) and ABTS(center dot+) (6.52 and 5.79 mu g/mL) scavengers, as well as AChE (221.33 and 110.26 mu g/mL), BChE (461.69 and 94.93 mu g/mL), alpha-glycosidase (206.86 and 220.00 mu g/mL) and alpha-amylase (189.86 and 200.86 mu g/mL) inhibitors. As a conclusion, both EEC and WEC had rich phenolic contents and demonstrated effective anticholinergic, antidiabetic and antioxidant effects.
- MakaleAçık Erişim2017Novel eugenol derivatives: Potent acetylcholinesterase and carbonic anhydrase inhibitors
Topal, Fevzi; Gulcin, Ilhami; Dastan, Arif; Guney, Murat
Eugenol was used as starting material to obtain some phenolic compounds. The synthesis of these phenolic compounds was performed in a two-step procedure. The structures of the formed products (novel eugenol derivatives 1–6) have been determined on the basis of NMR spectroscopy and other spectroscopic methods. The compounds were tested in terms of carbonic anhydrase (CA) inhibition potency. Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes, which catalyse the reaction between carbon dioxide (CO2) and water (H2O), to generate bicarbonate (HCO3−) and protons (H+). CO2, HCO3− and H+ are essential molecules and ions for many important physiologic processes occurring in all living organisms. Acetylcholinesterase (AChE, E.C.3.1.1.7) is found in high concentrations in the red blood cells and brain. Novel eugenol derivatives (1–6) were tested for the inhibition of two cytosolic CA isoforms I, and II (hCA I, and II) and AChE. These compounds demonstrated effective inhibitory profiles with Ki values in ranging of 113.48-738.69 nM against hCA I, 92.35-530.81 nM against hCA II, and 90.10-379.57 nM against AChE, respectively. On the other hand, acetazolamide clinically used as CA inhibitor, shoed Ki value of 594.11 nM against hCA I, and 120.68 nM against hCA II, respectively. Also, AChE was inhibited by tacrine as an AChE inhibitor at the 71.18 nM level.
- MakaleAçık Erişim2017Synthesis of some natural sulphonamide derivatives as carbonic anhydrase inhibitors
Gokcen, Taner; Al, Melike; Topal, Meryem; Gulcin, Ilhami; Ozturk, Turan; Goren, Ahmet C.
Carbonic anhydrase inhibitor; sulphonamides; p-hydroxybenzoic acid; 3,4,5-trihydroxybenzoic acid (gallic acid).Carbonic anhydrase inhibitors are both in clinical use as antiglaucoma, diuretics, antiepileptics and management of altitude sickness, and under investigation as anticancer, anticonvulsant and antiobesity agents. Sulphonamides have been known for decades as carbonic anhydrase inhibitors and are in clinical use. Sulphonamide derivatives of p-hydroxybenzoic acid and 3,4,5-trihydroxybenzoic acid (gallic acid) were synthesized and their inhibition values over hCA I and hCA II isozymes, purified from human erythrocyte cells by Sepharose-4B-L-tyrosine-sulphanilamide, were determined. Compounds synthesized showed efficient carbonic anhydrase inhibition activity at low nM levels.
- MakaleYayıncıda açık erişim2015Inhibition profile of a series of phenolic acids on bovine lactoperoxidase enzyme
Sarikaya, S. Beyza Ozturk; Sisecioglu, Melda; Cankaya, Murat; Gulcin, Ilhami; Ozdemir, Hasan
Lactoperoxidase (LPO) catalyzes the oxidation of numerous of organic and inorganic substrates by hydrogen peroxide. It has very vital activity in the innate immune system by decreasing or stopping the activation of the bacteria in milk and mucosal secretions. This study's purpose was to investigate in vitro effect of some phenolic acids (ellagic, gallic, ferulic, caffeic, quercetin, p-coumaric, syringic, catechol and epicatechin) on the purified LPO. This enzyme was purified from milk by using different methods such as Amberlite CG-50 resin, CM-Sephadex C-50 ion-exchange and Sephadex G-100 gel filtration chromatography. LPO was purified 28.7-fold with a yield of 20.03%. We found phenolic acids have inhibition effects on bovine LPO enzyme to different concentrations. Our study showed lower concentrations of caffeic acid, ferulic acid and quercetin exhibited much higher inhibitory effect on enzyme, so these three of them were clearly a more potent inhibitor than the others were. All of compounds were non-competitive inhibitors.